The BTB protein MEL-26 is a substrate-specific adaptor of the CUL-3 ubiquitin-ligase
The BTB protein MEL-26 is a substrate-specific adaptor of the CUL-3 ubiquitin-ligase
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DOI：
10.1038/nature01959
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发表时间：
2003-09-18
期刊：
影响因子：
64.8
通讯作者：
Peter, M
中科院分区：
文献类型：
--
作者：
Pintard, L;Willis, JH;Peter, M
许多生物过程，如发育和细胞周期的进展是严格控制的选择性泛素依赖降解的关键底物。在这个途径中，e3连接酶识别底物，并将其定位为26S蛋白酶体的降解目标。SCF （Skp1-Cul1-F-box）和ECS（拉长蛋白C-Cul2-SOCS box）复合物是两个定义明确的基于cullin的e3连接酶（1-3）。cullin亚基具有支架功能，分别通过其C端与RING-finger-containing蛋白Hrt1/Roc1/Rbx1相互作用，并通过其N端与Skp1或伸长蛋白C相互作用。在秀丽隐杆线虫中，在减数分裂到有丝分裂的过程中，微管切断蛋白MEI-1/katanin的降解需要cu -3复合物的泛素连接酶活性(4)。然而，这种基于cullin的e3连接酶的分子组成尚不清楚。在这里，我们发现含有btb的蛋白MEL-26是体内降解MEI-1所需的成分。重要的是，MEL-26在体内和体外与CUL-3和MEI-1特异性相互作用，并显示出底物特异性适配器的特性。我们的研究结果表明，含btb的蛋白通常在cul3 - e3泛素连接酶中作为底物特异性接头起作用。
Many biological processes, such as development and cell cycle progression are tightly controlled by selective ubiquitin-dependent degradation of key substrates. In this pathway, the E3-ligase recognizes the substrate and targets it for degradation by the 26S proteasome. The SCF (Skp1-Cul1-F-box) and ECS (Elongin C-Cul2-SOCS box) complexes are two well-defined cullin-based E3-ligases(1-3). The cullin subunits serve a scaffolding function and interact through their C terminus with the RING-finger-containing protein Hrt1/Roc1/Rbx1, and through their N terminus with Skp1 or Elongin C, respectively. In Caenorhabditis elegans, the ubiquitin-ligase activity of the CUL-3 complex is required for degradation of the microtubule-severing protein MEI-1/katanin at the meiosis-to-mitosis transition(4). However, the molecular composition of this cullin-based E3-ligase is not known. Here we identified the BTB-containing protein MEL-26 as a component required for degradation of MEI-1 in vivo. Importantly, MEL-26 specifically interacts with CUL-3 and MEI-1 in vivo and in vitro, and displays properties of a substrate-specific adaptor. Our results suggest that BTB-containing proteins may generally function as substrate-specific adaptors in Cul3-based E3-ubiquitin ligases.